Biomedical subjects

G Pless

Publications and source records attributed to G Pless.

6 recordsLinked to original sources

PubMed2006

Dynamics of amino acid metabolism of primary human liver cells in 3D bioreactors.

The kinetics of 18 amino acids, ammonia (NH3) and urea (UREA) in 18 liver cell bioreactor runs were analyzed and simulated by a two-compartment model consisting of a system of 42 differential equations. The model parameters, most of them representing enzymatic activities, were identified and their values discussed with respect to the different liver cell bioreactor performance levels. The nitrogen balance based model was used as a tool to quantify the variability of runs and to describe different kinetic patterns of the amino acid metabolism, in particular with respect to glutamate (GLU) and aspartate (ASP).

Amino Acids↗

PubMed2005

Bioartificial liver: current status.

Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

Humans↗

PubMed2003

Clinical extracorporeal hybrid liver support--phase I study with primary porcine liver cells.

The objective of this study was to evaluate the feasibility and safety of a hybrid liver support system with extracorporeal plasma separation and bioreactor perfusion in patients with acute liver failure (ALF) who had already fulfilled the criteria for high urgency liver transplantation (LTx). Eight patients (one male, seven female) were treated in terms of bridging to transplantation. The mean age was 36.5 yr (range 20 to 58). Etiology of liver failure was drug-related in two patients, hepatitis B infection in three patients, and unknown for three patients. The bioreactors were charged with primary liver cells from specific pathogen-free pigs. Cell viability varied between 91 and 98%. Continuous liver support treatment over a period of 8 to 46 h (mean 27.3 h) was safely performed and well-tolerated by all patients. No complications associated with the therapy were observed during the follow-up period. Thrombocytopenia was considered to be an effect of the plasma separation. Subsequently, all patients were transplanted successfully and were observed over at least 3 yr with an organ and patient survival rate of 100%. Screening of patient's sera for antibodies specific for porcine endogenous retroviruses (PERVs) showed no reactivity--either prior to application of the system, or after extracorporeal treatment. The results encourage us to continue the development of the technology, and further studies appear to be justified. The bioreactor technology has been integrated into a modular extracorporeal liver support (MELS) system, combining biologic liver support with artificial detoxification technology.

Adolescent↗

PubMed2002

Primary human liver cells as source for modular extracorporeal liver support--a preliminary report.

Cell-based extracorporeal liver support is an option to assist or replace the failing organ until regeneration or until transplantation can be performed. The use of porcine cells or tumor cell lines is controversial. Primary human liver cells, obtained from explanted organs found to be unsuitable for transplantation, are a desirable cell source as they perform human metabolism and regulation. The Modular Extracorporeal Liver Support (MELS) concept combines different extracorporeal therapy units, tailored to suit the individual and intra-individual clinical needs of the patient. A multi-compartment bioreactor (CellModule) is loaded with human liver cells obtained by 5-step collagenase liver perfusion. A cell mass of 400 g - 600 g enables the clinical application of a liver lobe equivalent hybrid organ. A detoxification module enables single pass albumin-dialysis via a standard high-flux dialysis filter, and continuous veno-venuous hemodiafiltration may be included if required. Cells from 54 human livers have been isolated (donor age: 56 +/- 13 years, liver weight: 1862 +/- 556 g resulting in a viability of 55.0 +/- 15.9%). These grafts were not suitable for LTx, due to steatosis (54%), cirrhosis (15%), fibrosis (9%), and other reasons (22%). Out of 36 prepared bioreactors, 10 were clinically used to treat 8 patients with liver failure. The overall treatment time was 7-144 hours. No adverse events were observed. Initial clinical applications of the bioreactor evidenced the technical feasibility and safety of the system.

Bioreactors↗

PubMed2002

Extracorporeal liver support: porcine or human cell based systems?

Initial results of the clinical use of primary porcine liver cells for extracorporeal liver support are being reviewed as the cell source is controversial. According to Eurotransplant data 20-25% of explanted donor livers are not transplanted, due to factors such as steatosis or cirrhosis. This number corresponds to the number of patients with acute liver failure who require bridging therapy to transplantation. Primary human liver cells from transplant discards can be isolated, purified and maintained in bioreactors and provide an alternative for cell-based extracorporeal liver support therapy. A four-compartment bioreactor enables recovery from preservation and isolation injury in a three-dimensional network of interwoven capillary membranes with integrated oxygenation, rendering the liver cells from these discarded donor organs viable for clinical utilization. Patient contact with additional animal-derived biomatrix and fetal calf serum can be avoided. The initiation of an in vitro cultivation phase allows cell stabilization, quality control, and immediate availability of a characterized system without cryopreservation. The hypothesis of this paper is that with appropriate logistics and four-compartment bioreactor technology, cells from human liver transplant discards can serve the demand for cell-based therapy, including extracorporeal liver support.

Animals↗

PubMed1999

Pharmacological aspects of N-acetyl-5-methoxytryptamine (melatonin) and 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (pinoline) as antioxidants: reduction of oxidative damage in brain region homogenates.

Oxygen consumption is a necessity for all aerobic organisms, but oxygen is also a toxic molecule that leads to the generation of free radicals. The brain consumes a high percentage of the oxygen inhaled (18.5%), and it contains large amounts of unsaturated fatty acids, which makes it highly susceptible to lipid peroxidation. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, is a free radical scavenger that was found to protect against lipid peroxidation in many experimental models. Another compound found in the pineal gland is pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline). Pinoline is structurally related to melatonin. Evidence suggests that pinoline may have an antioxidant capacity similar to that of melatonin. In this study, the ability of pinoline to protect against H2O2-induced lipid peroxidation of different rat brain homogenates (frontal cortex, striatum, cerebellum, hippocampus, and hypothalamus) was investigated. The degree of lipid peroxidation was assessed by estimating the levels of thiobarbituric acid reactive substances, malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA). Pinoline's antioxidant capacity was compared with that of melatonin. Both melatonin and pinoline reduced the level of MDA and 4-HDA in a dose-dependent manner in all brain regions tested. To compare the antioxidant capacities, percent-inhibition curves were created, and the IC50 values were calculated. The IC50 values for melatonin were higher in all brain regions than were those for pinoline. The IC50 values for melatonin in the five different brain regions ranged from 0.16 mM-0.66 mM, and for pinoline, they ranged from 0.04 mM-0.13 mM. The possibility of synergistic interactions between melatonin and pinoline were also determined using the method of Berenbaum. Little evidence for either synergistic, additive, or antagonistic interactions between melatonin and pinoline was found.

Animals↗